Abstract Investments in biomedical research have paid large dividends in the form of groundbreaking treatments for a host of diseases. Efforts to accelerate such benefits often assume there is a linear progression that begins with an understanding of basic biological principles, and then advances to therapeutic development, evaluation, and ultimately clinical application. As a result, many initiatives focus on the stages that follow discovery. The Dartmouth Institute for Biomolecular Targeting (iTarget) infuses even early-stage mechanistic investigation with a sophisticated awareness of translational possibilities. This approach will ensure that knowledge of disease pathology provides focus and context to enhance the impact of even the most fundamental research. At the same time, it targets mechanistic investigations in directions that increase the probability of ultimate translational success. iTarget is structured (1) to accelerate the research productivity and scientific impact of four exceptional junior faculty members with interrelated interests in biomolecular target identification, validation, and inhibition; (2) to provide a supportive framework for mentoring by experienced and committed senior faculty; (3) to develop essential shared research resources not available at Dartmouth or our regional IDeA partners and to facilitate access to existing cores; and (4) to recruit new faculty to the Institute. With faculty engagement from 10 departments across the Faculty of Arts and Sciences, Geisel School of Medicine, and Thayer School of Engineering, our initiative is truly multidisciplinary. Dartmouth's collegial and highly interactive faculty have outstanding strength in curiosity-based discovery, healthcare delivery and population-based outcomes analysis, and the university has made key investments in translational research. iTarget will thus benefit from natural research synergies that complement, but do not overlap with our programmatic partners. In return, iTarget fills a critical role, bringing researchers together at the interface between basic and translational sciences. It will thus stimulate interdisciplinary and innovative research projects to address unmet therapeutic needs. It will also enhance the regional research infrastructure, providing cutting-edge strategies for generating proteins and other molecular targeting tools and for visualizing molecular interactions in purified systems and in cells. The He recovery system to be purchased with the funds requested in this supplement, will ensure the long-term sustainability of the NMR facility, one of the fundamental resources supported by iTarget, which enables cutting edge research by a number of NIGMS funded faculty.